The objective of this study is to analyze mechanism of development of experimentally induced emphysema. This will be done primarily by understanding when and how the reactions to injury or injury itself which leads to emphysema is different from reactions or injury which leads to "normal repair." Currently the effect of nitrogen dioxide (NO2) exposure on urinary glosides of hydroxylysine peptides derived from collagen catabolism are being studied to provide an index of the time of onset, severity and conclusion of collagen injury. Total collagen and elastin content of the lungs at various intervals following NO2 exposure are being analyzed. Preliminary results indicated that the total collagen and elastin content decrease within 24 hours after NO2 (30ppm) are lowest on the 7th day and return to control values 2 weeks after exposure has started-in spite of the continuation of NO2 exposure for the entire two week period. A standard model of aerosol induced elastase emphysema is being developed with a new recirculating aerosol chamber. The elastase aerosol model or alternatively an intratracheal elastase model will be used to test in vivo activity of chloromethylketone inhibitors (acetyl-alanyl-alanyl-prolyl-alanyl-chloromethylketone (AAPACMK) of elastase activity by study of their inhibitory effect on elastase induced emphysema. Leucocytes collected from the peritoneal cavity of the rabbit have been used to obtain, concentrate and analyze neutrophil elastase. The granules of these cells contain 1.39 micrograms of elastase/10 to the 8th power cells. Further studies will be performed to see if the elastase content of the leucocytes can be increased. The effect of AAPACMK on leucocyte elastase will be studied. The ability of leucoyte elastase to produce experimental emphysema by inoculation intratracheally in homologous or isologous hosts will be tested. Finally the response of the APUD (K cells) of lung in injury and repair will be studied and their function evaluated. BIBLIOGRAPHIC REFERENCES: Liotta, L.A., Saidel, G.M., and Kleinerman, J.: A Stochastic Model of Metastasis Formation. Biometrics. 32: 535-550, 1976. Saidel, G.M., Liotta, L.A., and Kleinerman, J.: System Dynamics of a Metastatic Process from an Implanted Tumor. J. Theoretical Biology. 56:417, 1976.